Moist wound dressings are products that cover wounds and keep the wounds in a moist environment. Moist wound dressings have been developed for recent 20 or more years at a greater speed than they had been developed over the previous hundred or more years. Many clinical results on moist wound dressings have revealed the stability and efficiency of a moist environment provided by the moist wound dressings in the treatment of chronic wounds, which have been considered as being impossible to treat, as well as acute wounds.
Epithelial cells are regenerated without any particular difficulty along the surface of wounds in a moist environment. In contrast, epithelial cells are not regenerated along the surface of wounds in a dry environment, and instead, form routes under the skin, which is a moist environment, and are regenerated along the routes. Accordingly, regeneration of epithelial cells in a dry environment is retarded, and thus the wound healing becomes inefficient. In a dry environment, substances involved in wound healing, such as polymorphonuclear leukocytes, macrophages, proteases and cell growth factors, contained in wound exudate are released to the outside or dried, thus impeding their inherent functions. In contrast, a moist environment allows the substances to successfully perform their functions, leading to efficient wound healing.
Silver has been empirically recognized over the past several centuries for its excellent antimicrobial activity and sterilizing power in comparison with other heavy metals. With the advance of modern sciences since the early twentieth century, the antimicrobial activity of silver and its mechanisms have been scientifically verified through systematic research conducted by many scientists.
Since the discovery of the first antibiotic, penicillin, bacteria resistant to penicillin have been reported. Many research results reveal that an extremely small amount of silver shows sufficiently effective antimicrobial activity against bacteria, such as the so-called superbacteria, resistant to methicillin and vancomycin, which is known as most effective antibiotic among those hitherto developed after penicillin, and possess broad spectrum antimicrobial effects against bacteria, including gram-positive and gram-negative bacteria, fungi and yeasts. Particularly, based on the fact that no silver-resistant bacteria have hitherto been reported, it is known that silver has less problems of resistance than other antimicrobial agents.
Such advantages of silver have been most successfully utilized in medical products. Development of nanotechnology since the early twenty-first century has provided a background for the efficient use of expensive silver from both technical and economic viewpoints. Taking advantage of the public's interest in the so-called well-being syndrome, development of products based on silver nanotechnology has been booming. Of these products, representative medical-related products are antimicrobial wound dressings for the treatment of acute wounds, e.g., burns, and chronic wounds, e.g., decubitus ulcers and diabetic foot ulcers.
Since serious burns of second-degree or higher and chronic wounds destroy the body protection functions of skin, bacterial infection of the wound sites occurs and/or a large amount of wound exudate is continuously secreted from the wound sites. Such bacterial infection makes the depth of the wound deeper. As the average human life has recently increased, the number of old patients with various kinds of chronic wounds has been rapidly increased.
Representative therapeutic methods for treating chronic wounds are associated with the use of antimicrobial agents for external application to treat and prevent bacterial infection and the use of wound dressings capable of absorbing wound exudate. Thus, there is an urgent need for an economically advantageous antimicrobial moist wound dressing that provides sufficient antimicrobial activity and is capable of effectively absorbing wound exudate.
Commercially available wound dressings using silver can be categorized into the following products.
The first products are dry wound dressings in which finely divided silver nanoparticles, e.g., nanocrystalline silver, prepared by nanotechnology are electrically coated on a polyurethane mesh fiber having a monolayer structure, and their similar products (U.S. Pat. Nos. 6,719,987 and 6,087,549). Since these products contain an excessively large amount of silver, they show superior antimicrobial activity, but are highly cytotoxic to normal cells. In addition, another disadvantage of the products is that the silver tends to fall off from the products, leading to temporary discoloration of applied skin sites. Furthermore, the products need wetting with distilled water before use, causing inconvenience in use. Moreover, since the products have a low exudate absorption capacity, they do not provide a sufficient moist environment.
The second products are wound dressings in which nanometer-sized silver precipitated by a chemical reaction is physically diffused or dispersed between fiber tissues, and their similar products (U.S. Pat. No. 6,897,349). These products provide a moist environment due to their high absorption capacity, but do not exert sufficient antimicrobial activity because of their low silver content. As a result, the products disadvantageously fail to achieve desired therapeutic effects.
Cream or gel type products (e.g., Flamazine) containing 1% of highly toxic silver nitrate, are also known. Although these products show superior antimicrobial activity as antimicrobial agents for external application, they are highly cytotoxic due to their high silver content and have no absorption capacity in view of their intrinsic characteristics.
The aforementioned products developed based on silver nanotechnologies have some problems in their structures in that the size and shape of nanoparticles are non-uniform, the distribution of particles is not readily controlled, control of the silver concentration and content is difficult, and high production costs are required. In addition, since silver is not chemically bonded but physically attached to the products, the finely divided silver nanoparticles become likely to fall off from the products. The fallen silver particles show high toxicity to not only various species of harmful bacteria but also normal human cells, thus causing serious health problems in humans.
Some research results show that the use of an extremely low concentration of silver for the treatment of burns results in about a five-fold increase in the metabolism rate of cells. If the silver is used in an amount exceeding the antimicrobial activity sufficient to treat infection, high cytotoxicity to normal cells is caused, thus posing a health hazard to humans. Consequently, in the case where products highly susceptible to falling of finely divided silver particles, which are developed based on silver nanotechnology, are directly used on the surface of wounds whose body protection functions are destroyed, the silver particles may be accumulated on respective human organs or easily penetrated into cells, thus being toxic to the cells. In this case, there exists a risk of causing life-threatening results.
There have been a series of research reports on the so-called Nano-ecology concerning the possibility that nanoparticles may adversely affect human health. Further, the safety of nanotechnology has been continuously questioned. Under these circumstances, the use of wound dressings produced by silver nanotechnology should be seriously reconsidered in view of potential dangers of the products. Moreover, excessive use of silver is economically disadvantageous and is environmentally unfriendly.
On the other hand, enclosed-type moist dressings employ hydrophilic polymers, such as hydrocolloids, hydrogels, polyurethane and calcium alginate, to absorb wound exudate so that a moist environment is provided and thus superior therapeutic effects are achieved. However, since these products contain no pharmacologically effective ingredient, they cannot be used on infected wound sites. In addition, the products cannot be combined with antimicrobial agents for external application, which impedes the growth of skin regenerative cells. Furthermore, the products have a disadvantage in use that bacteria must be previously removed from infected wounds.
More seriously, moist environment provides an optimal environment in which bacteria can proliferate and grow. Although there is little possibility of bacterial infection in clean wound sites, people having limited medical knowledge on wound infection are exposed to unexpected additional risks, such as aggravation of wound sites resulting from infection and increased treatment period and costs. Therefore, there is a demand to improve the limited functions, such as prevention of secondary infection from the environment, protection of wounds and provision of a moist environment, of currently available enclosed-type moist wound dressings by imparting antimicrobial activity to the wound dressings.